Neurotrophic factors for the treatment of Parkinson's disease

Parkinson's disease (PD) is a common neurodegenerative disorder caused by the progressive degeneration of the nigrostriatal dopaminergic pathway. The resulting loss of dopamine neurotransmission is responsible for the symptoms of the disease. Available treatments are initially successful in treating PD symptoms; however, their long-term use is associated with complications and they cannot stop the neurodegeneration. Current research aims at developing new therapies to halt/reverse the neurodegenerative process, rather than treating symptoms. Neurotrophic factors are proteins critical for maintenance and protection of neurones in the developing and adult brain. Several neurotrophic factors have been investigated for their protective effects on dopaminergic neurones. Here we review some of the most promising factors and provide an update on their status in clinical trials.

► Neurotrophic factors have therapeutic potential for Parkinson's disease (PD).
► The most promising factors are GDNF family ligands, GDF5 and MANF/CDNF.
► We review studies on these factors in in vitro and in vivo models of PD.
► We describe clinical trials that used GDNF and neurturin in PD patients.
► We discuss limitations and future directions in neurotrophic factor therapy for PD.